Many skin lightening methods and compositions have been reported. Actives which are known for skin lightening can be prepared synthetically or may be used or extracted from natural sources. These actives can be used for skin lightening in general and also to treat, prevent or improve appearance of skin against hyperpigmentation, age spots, blemishes etc.
Skin color is determined by the amount, type and distribution of melanin within the epidermal cells. Keratinocytes are the major cells in the skin epidermis (>90% of the population) while fibroblasts are situated in the dermis and melanocytes (˜5% of the total epidermal cells) are present at the dermal: epidermal junction. These three types of cells communicate with each other through various secreted factors to regulate skin pigmentation.
Melanocytes in skin synthesize melanin (a biopolymeric pigment) and transfer it to neighbouring keratinocytes, for distribution of melanin within the upper layers of the skin. Melanin is synthesized inside specialized lysosome-related organelles, termed melanosomes. Skin color is influenced by several factors including (a) the amount and types of melanin produced and transferred to keratinocytes and (b) its subsequent incorporation, aggregation and degradation within keratinocytes. Other factors that regulate skin pigmentation include factors secreted from keratinocytes and fibroblasts that affect melanocytes, endocrine factors from the blood supply, as well as neural factors and inflammation-related factors; extrinsic factors that affect skin pigmentation include ultraviolet (UV) radiation. Regulating some of these factors using siRNA have been reported.
siRNA are short double stranded small interfering RNA molecules. Most of the siRNA are 20-25 nucleotides in length. siRNA are involved in RNA interference and regulate (interfere with—silence) gene expression, post-transcriptionally. Synthetic siRNA can be introduced into cells using appropriate transfection procedures and typically demonstrate transient effects. This results in sequence complementarity based knock down of the corresponding target gene's expression. The above mentioned characteristic length seems to maximize target gene specificity over non-specific effects. When a particular target gene is known, the overall process includes selective design of a few siRNA sequences to target various parts of that gene and test out experimentally, to identify the most efficacious siRNA sequence(s) within that set (highest suppression of gene expression). The relevance of a given gene vis-à-vis a particular cellular phenomenon can be tested out using siRNA against that gene. siRNA thus serves both as an examination tool in the study gene function as well as a technology handle to modulate gene expression and through that, cellular physiology.
Oligonucleotides have been disclosed for depigmentation of skin e.g. in U.S. Pat. No. 7,087,743, U.S. Pat. No. 7,504,385, and US 2007/0134188. The oligonucleotides claimed in the present invention have not been disclosed in the above publications or any other published document for inclusion in a composition for application on skin.
A very large number of siRNA molecules for gene expression inhibition have been reported in EP1752536, EP2213738, WO2009/001359, and WO2010/080452 with possible use in pharmaceutical applications. However, none of them teach or direct one to use any of those oliogonucleotides for application on skin for skin lightening benefit.
It is thus an object of the present invention to provide for novel oligonucleotides that provide enhanced skin lightening efficacy.